Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.
Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline, dopamine, and serotonin-in patients with obesity.



We undertook a phase II, randomised, double-blind, placebo-controlled trial in five Danish obesity management centres. After a 2 week run-in phase, 203 obese patients (body-mass index 30-</=40 kg/m(2)) were prescribed an energy restricted diet and randomly assigned with a list of randomisation numbers to treatment with tesofensine 0.25 mg (n=52), 0.5 mg (n=50), or 1.0 mg (n=49), or placebo (n=52) once daily for 24 weeks. The primary outcome was percentage change in bodyweight. Analysis was by modified intention to treat (all randomised patients with measurement after at least one dose of study drug or placebo). The study is registered with ClinicalTrials.gov, number NCT00394667.



161 (79%) participants completed the study. After 24 weeks, the mean weight loss produced by diet and placebo was 2.0% (SE 0.60). Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p<0.0001). The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia. After 24 weeks, tesofensine 0.25 mg and 0.5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo, whereas heart rate was increased by 7.4 beats per min in the tesofensine 0.5 mg group (p=0.0001).



Our results suggest that tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved drugs. However, these findings of efficacy and safety need confirmation in phase III trials.
Astrup
Arne
A
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark. Electronic address: ast@life.ku.dk.
Madsbad
Sten
S
Department of Endocrinology, University of Copenhagen, Denmark.
Breum
Leif
L
Department of Medicine, Køge Hospital, Køge, Denmark.
Jensen
Thomas J
TJ
Cyncron Clinical Research Unit, Copenhagen, Denmark.
Kroustrup
Jens Peter
JP
Department of Endocrinology, Aalborg Hospital, Aalborg, Denmark.
Larsen
Thomas Meinert
TM
Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark.
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000627:therapeutic use*; D031204:Caloric Restriction; D003718:Denmark; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy*; D011788:Quality of Life; D015431:Weight Loss; D055815:Young Adult
D019440:Anti-Obesity Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C518479:Tesofensine